aminopterin / Syntrix - LARVOL DELTA

Antifolate agent aminopterin demonstrates potent anti-monkeypox virus activity in vitro and in vivo. (PubMed, Microbiol Spectr) - "It significantly inhibited MPXV replication, unlike other antifolate agents such as methotrexate, pemetrexed, and LSN3213218. Crucially, aminopterin suppresses viral infection and mitigates infection-associated inflammation in vivo. These findings position aminopterin as a potential candidate for the development of an antiviral agent against MPXV."

Journal • Preclinical • Infectious Disease • Oncology

Pralatrexate is a potent pan-serotype human adenovirus inhibitor through suppression of dihydrofolate reductase. (PubMed, Antimicrob Agents Chemother) - "In this study, three folate antagonists aminopterin (AMT), pralatrexate (PDX), and methotrexate (MTX) with potent antiviral activity against HAdV infection have been identified through a drug repurposing screening strategy. Mechanistic studies revealed that PDX achieved its antiviral activity through suppression of dihydrofolate reductase (DHFR). These findings support the potential of folate antagonists as repurposed therapeutic agents against HAdV infection and provide a rationale for the development of host-directed antiviral strategies."

Journal • Infectious Disease • DHFR

Erratum: Evolution of Therapy in Pediatric ALL From Aminopterin to Chimeric Antigen Receptor T-Cell Therapy: Global Advances, Indian Adaptations, and Lessons for Low- and Middle-Income Countries. (PubMed, JCO Glob Oncol) - No abstract available

Journal • Pediatrics

Quantifying Epigenetic Changes Induced by Chemical Exposure Using the epi-TK Assay. (PubMed, Bio Protoc) - "Following chemical exposure, epigenetic perturbations at the TK locus are detected by culturing cells under hypoxanthine-aminopterin-thymidine selection and quantifying the frequency of TK revertant colonies, which reflects restoration of TK gene expression...• By employing a DNA-methylated housekeeping TK gene and colony formation as the readout, the assay enables quantitative epigenetic changes without the need for specialized equipment. • The protocol offers a simple, quantitative, and cost-effective platform that is suitable for routine testing and comparative assessment of multiple compounds."

Journal • Oncology • DNMT1

Evolution of Therapy in Pediatric ALL From Aminopterin to Chimeric Antigen Receptor T-Cell Therapy: Global Advances, Indian Adaptations, and Lessons for Low- and Middle-Income Countries. (PubMed, JCO Glob Oncol) - "The care of childhood ALL in India demonstrates how evidence-based protocol adaptations, health system strengthening, and multicentric collaboration can improve outcomes in LMICs despite several challenges, including financial constraints, limited drug access, late presentation, and treatment abandonment."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • Pediatrics

STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis. (PubMed, Mol Cancer) - "STK3 was identified as a transcriptional target of YAP1, leading to enhanced DNA repair ability and stemness acquisition during GC progression by activating Wnt/β-catenin activity through GSK-3β degradation. Moreover, STK3-targeted therapy offered a novel approach to concur acquired chemo-resistance in GC patients."

Journal • Gastric Cancer • Oncology • Solid Tumor • YAP1

Heterohybridomas producing human immunoglobulin light chains using CD138-selected bone marrow cells. (PubMed, Biochem Biophys Rep) - "Marrow CD138+ cells from patients with multiple myeloma (MM) and polyclonal gammopathy (PG) were selected, fused with B5-6 T cells and cultured in hypoxanthine-aminopterin-thymidine medium (HAT)...With IP in vivo implants after 2 weeks more dimers were seen than in short term cultures in vitro. These HH clones will be made available for study of FLC metabolism and testing of therapeutics designed to abrogate FLC production or enable FLC clearance in vivo."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

Establishment of B4-100 and B4-C4, clonal canine multiple myeloma cell lines and their application in generating monoclonal antibody-producing fully canine hybridomas. (PubMed, Vet Immunol Immunopathol) - "The cells were found to express IgE in the cell lysate by western blotting but did not express HGPRT, and were unable to grow in hypoxanthine-aminopterin-thymidine medium. When the cells were fused with canine peripheral blood mononuclear cells in vitro, hybridomas producing canine immunoglobulins in the culture supernatant could be generated. To our knowledge, this is the first report on establishment of canine myeloma cell lines and we submit that these cell lines may provide opportunities for the production of fully caninized antibodies with potential for therapeutic applications."

Journal • Preclinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

Effect of Single and Multiple Methotrexate Doses Treatment on Ovarian Reserve in Ectopic Pregnancy Women: A Prospective Cohort Study. (PubMed, J Obstet Gynaecol India) - "There was only a statistically significant difference in estradiol levels between the two groups (P: 0.02), and estradiol concentrations were higher in the multiple-dose MTX group. Administration of MTX (regardless of number of doses) has no negative effect on ovarian reserve and is safe to be used as a treatment for EP."

Journal

Innovative approaches in QSPR modelling using topological indices for the development of cancer treatments. (PubMed, PLoS One) - "The analysis covers a range of Cancer drugs, including Aminopterin, Convolutamide A, Convolutamydine A, Daunorubicin, Minocycline, Podophyllotoxin, Caulibugulone E, Perfragilin A, Melatonin, Tambjamine K, Amathaspiramide E, and Aspidostomide E. The findings demonstrate that optimal regression models (Fifty-eight models) incorporating TI can effectively predict physicochemical properties, such as Boiling Point (BP), Enthalpy (EN), Flash Point (FP), Molar Refractivity (MR), Polar Surface Area (PSA), Surface Tension (ST), Molecular Volume (MV), and Complexity (COM). This research suggests that temperature-based topological indices (TI) are promising tools for the development and optimization of cancer drugs, as demonstrated by statistically significant results with a p-value less than 0.05. In addition to the linear regression model, which performed the best, two other machine learning models, namely SVR and Random Forest, were also used for further analysis and comparison..."

Journal • Review • Oncology

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy. (PubMed, Cureus) - "In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia...Farber also introduced actinomycin D to treat Wilms tumor in various stages...Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted."

Journal • Review • Hematological Malignancies • Leukemia • Nephrology • Oncology • Pediatrics • Solid Tumor • Wilms Tumor

Generation of monoclonal antibody against 6-Keto PGF1α and development of ELISA for its quantification in culture medium. (PubMed, Biochem Biophys Rep) - "Then, fusion of antibody-producing spleen lymphocytes with SP-2 myeloma cells and thymocytes was performed and cultured in HAT-medium supplemented with hypoxanthine, aminopterin, and thymine...A standard ELISA calibration curve was developed with 100% reactivity for 6-Keto-PGF 1 α ranging from 0.26 pg to 6.44 ng corresponding to 90% and 10% of the maximum binding capacity for the immobilized antigen respectively. This method can easily be applied to monitor PGI2 regulation in different stages of cultured adipocytes to reveal the regulatory roles of PGI2 in maintaining homeostasis and adipocyte differentiation."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Shedding light into the biological activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses. (PubMed, J Biomol Struct Dyn) - "The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • DHFR

Arsenic to biologics: psoriasis treatment through the ages (BAD 2023) - "In 1951, a patient with rheumatoid arthritis showed dramatic improvement in their psoriasis when treated with aminopterin, as recorded by Richard Gubner, a New York cardiologist. PUVA was developed in the 1970s—a photochemotherapy for psoriasis that combined psoralen with UVA radiation to clear skin lesions...Furthermore, in the 1980s, researchers noted complete clearance of psoriasis in a patient with osteoporosis who was prescribed an oral form of vitamin D. This chance observation then led to the development of topical vitamin D analogues for the treatment of psoriasis that work by encouraging normal skin growth and slowing down overproduction of skin cells. Finally, in 2003, the first biologic treatments were approved for psoriasis by the US Food and Drug Administration—a significantly safer and more efficacious alternative to the controversial arsenic treatments that were used over 200 years ago."

Cardiovascular • Dermatology • Immunology • Inflammatory Arthritis • Osteoporosis • Psoriasis • Rheumatoid Arthritis • Rheumatology • Vitiligo

Identification of Unique and Conserved Neutralizing Epitopes of Vestigial Esterase Domain in HA Protein of the H9N2 Subtype of Avian Influenza Virus. (PubMed, Viruses) - "After Hypoxanthine-Aminopterin-Thymidine (HAT) medium screening and indirect ELISA detection, six hybridoma cell lines producing anti-HA monoclonal antibodies were screened...Epitope NVENLEEL has a partial amino acid crossover with EELRSLFS, which is located in the vestigial esterase domain "110-helix" of HA, and the monoclonal antibody recognizing these epitopes showed the neutralizing activity, suggesting that the region NVENLEELRSLFS might be a novel neutralizing epitope. The results of the homology analysis showed that these three epitopes were generally conserved in H9N2 subtype AIV, and will provide valuable insights into H9N2 vaccine design and improvement, as well as antibody-based therapies for treatment of H9N2 AIV infection."

Journal • Infectious Disease • Influenza • Respiratory Diseases

"The first drug being Aminopterin.. n then came Amethopterin (methotrexate).. had framed 2 questions in the recent quiz and one went completely unanswered.." (,@drhemanthmd1)

Development of HPV58 type-specific antibodies and detection kit. (PubMed, Prep Biochem Biotechnol) - "Finally, an enzyme-linked immunosorbent assay (ELISA) detection kit was assembled with 2F7 and 2G7 mAbs which possessed high specificity to HPV58 L1-VLPs. The detection kit developed by 2F7 and 2G7 could be adopted to specifically detect HPV58 L1 protein with good linearity and detection range, which could be widely used in clinical testing and quality control in the production of HPV vaccines.Abbreviations: BSA: Bovine serum albumin; CDRs: Complementarity-determining regions; CV: Coefficient of variation; DTT: Dithiothreitol; ELISA: Enzyme-linked immunosorbent assay; HAT: Hypoxanthine-aminopterin-thymidine; HPV: Human Papillomavirus; IC: 50% inhibition rate; IC: 90% inhibition rate; mAbs: Monoclonal antibodies; VLP: Virus-like particle."

Journal • Oncology

The first achievement of complete remission in childhood leukemia by treatment with the folic acid antagonist aminopterin. (PubMed, Haematologica) - No abstract available

Journal • Hematological Malignancies • Leukemia • Oncology

Monoclonal antibodies to activated CDK4: use to investigate normal and cancerous cell cycle regulation and involvement of phosphorylations of p21 and p27. (PubMed, Cell Cycle) - "Moreover we demonstrated that the highly variable detection of T172-phosphorylated CDK4 signals the presence or absence of the active CDK4 targeted by the CDK4/6 inhibitory drugs, which predicts the tumor cell sensitivity to these drugs including palbociclib. The specific immunoprecipitation of T172-phosphorylated CDK4 allowed to clarify the involvement of phosphorylations of co-immunoprecipitated p21 and p27, showing a privileged interaction of T172-phosphorylated CDK4 with S130-phosphorylated p21 and S10-phosphorylated p27. Abbreviations: 2D: two-dimensional; CAK: CDK-activating kinase; CDK: cyclin-dependent kinase; HAT: Hypoxanthine-Aminopterin-Thymidine; FBS: fetal bovine serum; IP: immunoprecipitation; ID: immunodetection; mAb: monoclonal antibody; PAGE: polyacrylamide gel electrophoresis; PBS: phosphate buffer saline; pRb: retinoblastoma susceptibility protein; SDS: sodium dodecyl sulfate; DTT: dithiotreitol; TET: tetracyclin repressor; Avi: Avi tag; TEV: tobacco..."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Eye Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • CDK4 • CDKN1A • ENO1 • ER

Targeting folate receptor beta on monocytes/macrophages renders rapid inflammation resolution independent of root causes. (PubMed, Cell Rep Med) - "Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation...We further show that EC2319 suppresses interleukin-6/interleukin-1β release by FRβ monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development."

Journal • Glomerulonephritis • Immunology • Inflammation • Lupus Nephritis • Nephrology • Ocular Inflammation • Ophthalmology • Rheumatology • Uveitis • IL1B • IL6

Recent developments in the medicinal chemistry of single boron atom-containing compounds. (PubMed, Acta Pharm Sin B) - "In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Leukemia • Multiple Myeloma • Nephrology • Novel Coronavirus Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Tuberculosis

A Novel Treatment for Glomerular Disease: Targeting the Activated Macrophage Folate Receptor with a Trojan Horse Therapy in Rats. (PubMed, Cells) - "Using a macrophage-mediated anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in WKY rats, we investigated the effect of a novel folic acid-aminopterin (AMT) conjugate (EC2319) designed to intracellularly deliver AMT via the FR...Notably, treatment with methotrexate (MTX), another folic acid antagonist related to AMT, did not protect from kidney damage...In nephritic kidneys, FRβ was expressed on periglomerular macrophages and macrophages present in the crescents, but its expression was not observed in normal kidneys. These data indicate that selectively targeting the activated macrophage population could represent a novel means for treating anti-GBM GN and other acute crescentic glomerulonephritis."

Journal • Preclinical • Fibrosis • Glomerulonephritis • Immunology • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • CCL2 • TGFB1

[VIRTUAL] Disclosure of PfMRP1 as an Influx ABC Transporter Protein in Plasmodium falciparum (WMF 2021) - "In this study, we demonstrate that edited generated pfmrp1 disrupted parasites are resistant to methotrexate and aminopterin, which are folate analogs with antimalarial activity. Here, PfMRP1 is demonstrated as an unexpected eukaryote importer ABC transporter, a novel function in this organism and uncommon in eukaryotes. These findings highlight the clear need to identify transporter mechanisms of ABC transporters."

Infectious Disease • Malaria • ABCC1

Liddle syndrome: A case report. (PubMed, Med Clin (Barc)) - "The patient is an atypical case of Liddle syndrome; genetic analysis is helpful and essential for diagnosis."

Clinical • Journal • Endocrine Disorders • Genetic Disorders • Hypertension • Nephrology

Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis (clinicaltrials.gov) - P2; N=19; Completed; Sponsor: Syntrix Biosystems, Inc.; Active, not recruiting ➔ Completed; Trial completion date: May 2021 ➔ Jan 2021

Clinical • Trial completion • Trial completion date • Dermatology • Immunology • Psoriasis